Human Skin is composed of three primary layers: the epidermis, which provides waterproofing and serves as a barrier to infection; the dermis, which serves as a location for the appendages of skin; and the hypodermis, which is called the basement membrane.
Skin disorder is related to epidermis, the outermost layer of the skin. It can be due to bacterial, viral, or fungal infections. Skin disorders can be a sign of imbalance in the body system.
Psoriasis is a non-contagious disorder which affects the skin and joints. The scaly patches caused by psoriasis, called psoriatic plaques, are areas of inflammation and excessive skin production. This disorder is a chronic recurring condition which varies in severity from minor localised patches to complete body coverage. There are many treatments available, but because of its chronic recurrent nature, psoriasis is a challenge to treat.
Pathophysiologically, one component of psoriasis not often focused upon is the presence of a defective skin barrier in psoriasis. Because of the rapid epidermal turnover, replacing the epidermis once every 4 days in active psoriasis, psoriatic patients possess a defective skin barrier with barrier function resembling that of the jellyfish. In contrast in normal skin, the epidermis is replaced once every 28-30 days. This result in stratum corneum which has a much better barrier function that does not allow water to escape or chemicals and bacteria to penetrate. The body is thus better protected from further injury and infection.
Psoriasis, skin wounds, acne, burns, eczema, and smoking-induced injuries are important pathological conditions of skin. Although many treatments currently exist for these conditions, there is a need for more effective treatments, particularly in dealing with superficial bacterial overgrowth by Staphylococcus aureus in conjunction with some of these conditions.
These conditions are frequently accompanied by inflammation, which can be mediated by a number of inflammatory cytokines secreted by inflammatory cells such as lymphocytes and macrophages, and by a number of locally or regionally acting substances, such as histamine, bradykinin, serotonin, the prostaglandins, thromboxanes, leukotrienes, and platelet-activating factor. However, these conditions share the same platform or pathological mechanism that is inflammation. Particularly, understanding the important inflammatory mechanism will help to understand the basis for psoriasis and the association of inflammatory diseases and other conditions in order to develop more effective treatments for skin damages such as wounds, burns, eczemas and acne.
In non-psoriatic subjects, inflammation can also be induced by a variety of infectious or allergic stimuli in diseases such as acne and eczemas, as well as by a variety of physical and chemical stimuli, such as burns, wounds, smoking/nicotine-induced injury and sun-induced skin damage leading to premature aging. These non-psoriatic inflammatory lesions also show increased levels of phosphorylase kinase. The increased glycogen breakdown resulting from increased activity of phosphorylase kinase ensures increased ATP stores for the multiple energy-dependent processes in the inflammatory cascade in these conditions.
In spite of clear biochemical and genetic origins of psoriasis as well as the pathology of acne, eczemas, burns, wounds, smoking/nicotine-induced injury, sun-induced skin damage and premature aging, and other conditions causing damage to the tissues through inflammation, there is still a need for more effective pharmaceutical compositions as well as effective treatments for psoriasis, acne, eczemas, wounds, burns, smoking/nicotine-induced damage, sun-induced damage and premature aging, as well as other conditions causing damage to the tissues through inflammation. In particular, there is a need for effective compositions as well as treatments that can reduce inflammation on the target site and those that are effective in situations in which there is bacterial overgrowth, as well as a need for treatments that can decrease the excessive scar tissue and detrimental proliferative response to skin and blood vessels in response to injury. In particular, smoking and sun-induced inflammatory damage can also promote premature aging. Inhibition of inflammation in these conditions, i.e., by inhibition of phosphorylase kinase activity, may prevent premature aging in sun-damaged skin and in the skin of chronic smokers. The timely treatment of burns and scalds by phosphorylase kinase inhibitors may decrease or prevent the development of excessive scarring.
There are many synthetic drug products available in market for treatment of psoriasis however, because of its chronic recurrent nature; psoriasis is a challenge to treat.
U.S. Pat. No. 6,515,016 describes a method for treating or preventing psoriasis, comprising administering to a patient in need thereof a therapeutically effective amount of an anti-microtubule agent, wherein said anti-microtubule agent is paclitaxel, or an analogue or derivative thereof.
U.S. Pat. No. 6,107,349 discloses a method for treating psoriasis in a human patient comprising administering to said patient by oral ingestion on a continuing basis therapeutic amounts in combination of Vitamin E evening primrose oil, folic acid and B-complex vitamins selected from the group consisting of Vitamin B-1, Vitamin B-2 Vitamin 3, Vitamin B-6, Vitamin B-12, biotin, para amino benzoic acid and lipotropic factors.
U.S. Pat. No. 6,830,758 claims a water insoluble, protective, adhesive skin patch useful for treating or preventing psoriasis, dermatitis, and/or eczema.
Further, there is ample literature available on herbal compositions for the treatment of psoriasis. WO/2003/057133 provides a novel herbal composition containing the extracts of the leaves and/or stem of Argemone mexicana plant, optionally containing the extract of the fruits of Cuminum cyminum, which exhibits useful in vitro, in vivo and interesting immunological and pharmacological activities; a process for preparation thereof; and a method of treatment of psoriasis and related immunological and biological disorders by administration of the said novel herbal composition.
U.S. Pat. No. 5,925,376 describes a method for inhibiting proliferation and terminal differentiation of psoriatic epidermal cells comprising the step of contacting the psoriatic epidermal cells with curcumin administered in a dose and by a route selected from the group consisting of (a) oral administration from 250 mg to 2 g daily and (b) a topical semi solid dosage forms, ointment/cream/gel/lotions in the concentration of 0.1% to 10%, together with one to four additional compounds, each additional compound being selected from the group consisting of: (i) 1-alpha,25-dihydroxy vitamin D3 in the form of 0.005% ointment; (ii) etretinate administered in a dose of 25 mg from one to three times daily; (iii) diltiazem administered at a dose of 60 mg three times daily; and (iv) anthralin administered in an ointment or paste in a concentration of from about 0.1% to about 3% once or twice daily. v) collagen administered as an ointment/cream/gel.
US20080058426 describes a cream composition containing a mixture of tetrahydrocurcuminoids comprising 70-80% tetrahydrocurcumin, 15-20% tetrahydrodemethoxycurcumin, and 2.5-6.5% tetrahydrobisdemethoxycurcumin.
Curcumin has been found to be a selective phosphorylase kinase inhibitor (Reddy S, Aggarwal B B. Curcumin is a non-competitive and selective inhibitor of phosphorylase kinase. FEBS Lett 1994; 341:19-22).
It has also been shown that suppression of phosphorylase kinase activity with curcumin leads to resolution of psoriasis (Heng M C Y et al. Drug-induced suppression of phosphorylase kinase activity correlates with resolution of psoriasis as assessed by clinical, histological and immunohistochemical parameters. British Journal of Dermatology 2000; 143:937-949).
Various pharmaceutical compositions as well as therapies for psoriasis have recently been disclosed, albeit none address the compositions comprising Tetrahydroxy curcumin//Bis-O-Demethyl curcumin (BDMC), curcumin, curcuminoids, which is unique and an important aspect of the present invention.
Therefore, there is a need in the art to develop herbal formulations which will also address the issues including inflammation and free radical generation in the mammals. Accordingly, the current application is directed to a nanoemulsified topical formulations comprising curcumin, tetrahydroxycurcumin//Bis-O-Demethyl curcumin (BDMC) or any other curcuminoids either alone or in combinations together with one or more pharmaceutically acceptable excipients or inactive ingredients suitable for the treatment of psoriasis as well as inflammation, which is a major component of diseases such as and not limiting to, acne, eczema, skin wounds, burns, smoking/nicotine-induced injury, premature aging, and sun-induced damage.